BackgroundAcute lung injury (ALI) is considered to be the major cause of respiratory failure in critically ill patients. Clinical studies have found that in patients with sepsis and after hemorrhage, the elevated level of high mobility group box-1(HMGB-1) in their circulation is highly associated with ALI, but the underlying mechanism remains unclear. Extracellular HMGB-1 has cytokine-like properties and can bind to Toll-like Receptor-4 (TLR4), which was reported to play an important role in the pathogenesis of ALI. The aim of this study was to determine whether HMGB-1 directly contributes to ALI and whether TLR4 signaling pathway is involved in this process.MethodsRecombinant human HMGB-1 (rhHMGB-1) was used to induce ALI in male Sprague-Dawley rats. Lung specimens were collected 2 h after HMGB-1 treatment. The levels of TNF-α, IL-1β, TLR4 protein, and TLR4 mRNA in lungs as well as pathological changes of lung tissue were assessed. In cell studies, the alveolar macrophage cell line, NR8383, was collected 24 h after rhHMGB-1 treatment and the levels of TNF-α and IL-1β in cultured medium as well as TLR4 protein and mRNA levels in the cell were examined. TLR4-shRNA-lentivirus was used to inhibit TLR4 expression, and a neutralizing anti-HMGB1 antibody was used to neutralize rhHMGB-1 both in vitro and in vivo.ResultsFeatures of lung injury and significant elevation of IL-1β and TNF-α levels were found in lungs of rhHMGB-1-treated animals. Cultured NR8383 cells were activated by rhHMGB-1 treatment and resulted in the release of IL-1β and TNF-α. TLR4 expression was greatly up-regulated by rhHMGB-1. Inhibition of TLR4 or neutralization of HMGB1 with a specific antibody also attenuated the inflammatory response induced by HMGB-1 both in vivo and in vitro.ConclusionHMGB-1 can activate alveolar macrophages to produce proinflammatory cytokines and induce ALI through a mechanism that relies on TLR-4.

Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti-inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a “from bench to bedside” perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

The systematic review suggested significant advantages of stenting before extracorporeal shock wave lithotripsy compared to in situ extracorporeal shock wave lithotripsy in terms of Steinstrasse. However, stenting did not benefit stone-free rate and auxiliary treatment after extracorporeal shock wave lithotripsy, and it induced more lower urinary tract symptoms. More high quality, randomized controlled trials are needed to address this issue.

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To explore the superiority of radiomics analysis in the diagnostic performance of coronary computed tomography angiography (CCTA) for identifying myocardial ischaemia and predicting major adverse cardiovascular events (MACE). A total of 105 lesions from 88 patients who underwent CCTA and invasive fractional flow reserve measurement were collected as the training set, and another 31 patients with CCTA and clinical outcome information were used as the validation set. Conventional CCTA features included the stenosis diameter, length, Agatston score and high-risk plaque characteristics. After extracting and selecting radiomics features, the robustness of the radiomics features was examined, and then conventional and radiomics models were established using logistic regressions. The area under the receiver operating characteristic (ROC) curve (AUC) and Net Reclassification Index (NRI) were analysed to compare the discrimination and classification abilities between the two models in both the training and validation sets. A total of 1409 radiomics features were extracted, and three wavelet features were finally screened out. The robustness test showed good stability for the refined radiomics features. Compared with the conventional model, the radiomics model displayed a significantly improved diagnostic performance in the training set (AUC 0.762 vs. 0.631, 95% confidence interval [CI] 0.671-0.853 vs. 0.519-0.742, P = 0.058) but a slightly improved diagnostic performance in the validation set (AUC 0.671 vs. 0.592, 95% CI 0.466-0.875 vs. 0.519-0.742, P = 0.448). The NRI of the radiomics model was increased in both the training and validation sets (NRI 0.198 and 0.238, respectively). Quantitative radiomics analysis was feasible and might help to improve the diagnostic performance of CCTA but is still controversial for predicting MACE.